Tox Tuesday: Suvorexant

If you have trouble falling asleep at night or staying asleep long enough to get a good night’s rest, you’re not alone. According to recent statistics, approximately 50 million Americans are afflicted with sleep-related problems or disorders such as insomnia.

Essential to physical and emotional health, adequate sleep plays a role in helping the body recover from illness and injury and impacts quality of life. That’s why it’s no surprise that prescription drugs to treat sleep disorders like insomnia, are estimated to reach $1.8 billion by 2023. This figure is up from $1.4 billion in 2016, and according to reports will be aided in part by a relatively new drug known as suvorexant — the first of its class of orexin receptor antagonists.

Orexin receptor antagonists work by binding to the orexin-1 and −2 receptors in the brain and decreasing the neurotransmitter orexin, which promotes wakefulness. This is different than most traditional prescription sleeping pills, which do the opposite and work by increasing levels of GABA, a neurotransmitter that slows down brain activity.

First introduced in 2015, suvorexant is prescribed in doses of 10 mg before bedtime, with the intention of producing rapid onset sleep. It has been classified by the Drug Enforcement Administration (DEA) as a scheduled IV drug meaning it has a currently accepted medical use and a low potential for abuse relative to the drugs in the schedule III class. According to the classification, abuse of the drug may lead to limited physical or psychological dependence.

However, some medical professionals believe suvorexant should be seen as a more dangerous substance and questions of its usefulness, potential for misuse, and dangerous side effects have come into play. In addition, there have been reports of people performing complex tasks after taking the drug (such as driving) with little recollection of the events.

According to an analysis from two drug safety experts—Steven Woloshin, M.D., and Lisa M. Schwartz, M.D., both at the Geisel School of Medicine at Dartmouth, people who took a 15 mg or 20 mg dose of suvorexant every night for three months fell asleep just six minutes faster on average than those who got a placebo pill. And the suvorexant group slept only 16 minutes longer—6 hours and 12 minutes total versus 5 hours and 56 minutes for the placebo group.

Those small improvements in sleep didn’t translate to people feeling more refreshed. Instead, more people who took suvorexant reported feeling drowsy the next day compared with those who took a placebo.

In fact, the review states that two people who took the 20 mg dose the night before were so drowsy the next day they had to stop a driving test. Slightly more people in the suvorexant group were involved in driving accidents or got traffic tickets and reported hallucinations or sleep paralysis—a feeling that you can’t move or talk while falling asleep or awakening.

Furthermore, others are concerned that suvorexant has the potential to be abused in the form of a “date rape drug” and because it can take up to 72 hours to metabolize a single dose, the feeling of next-day prolonged drowsiness is a real concern.

Other experts, however, are less worried. “Nothing happened in the trials that made [suvorexant] look safer or more dangerous than other sleeping pills,” Dr. Thomas Roth, a sleep medicine expert, said in the article also noting that suvorexant’s safety profile “maintains the same precautions and warnings as other sleep medications on the market.”

Because of the new nature of the drug, the question of how it can be detected in a forensic setting has also come into play. Currently there are no commercially available metabolites and therefore no available immunoassays to pre-screen samples for this drug.

However, in the recent article: “Identification of Suvorexant in Urine using LC-Q/TOF-MS,” published in the Journal of Analytical Toxicology, an instrumental method is outlined for detection of that could meet validation standards required for forensic toxicology for the parent drug.

The article explains that due to its high boiling point (669°C), suvorexant is highly retained using gas chromatography, potentially eluting after data acquisition may have concluded using conditions that are commonly used for gas chromatographic screening (potentially greater than 30 minutes).

If your lab is interested in an ELISA test kit capable of screening for suvexorant, please contact Neogen’s product manager, Dan Grubb to discuss in more detail.